Enhanced procoagulant activity of platelets after chemotherapy in non-small cell lung cancer

Abstract

The procoagulant status of patients with non-small cell lung cancer (NSCLC) after chemotherapy is poorly characterized and the role of platelets in hypercoagulative state of NSCLC is unknown. The aim of this study was to evaluate the procoagulant activity (PCA) of platelets in NSCLC before and after chemotherapy. The subjects were 52 patients newly diagnosed with NSCLC. The patients had decreased clotting time compared with healthy subjects, and the thrombin-antithrombin complex increased 2.5-fold after chemotherapy. Platelets in the patients after chemotherapy had enhanced phosphatidylserine (PS) exposure, and shortened coagulation time as well as increased thrombin and fibrin formation of platelets compared with those before chemotherapy. Platelet-derived microparticles increased 2-fold at day 1 and peaked at day 2 post-chemotherapy. Treatment of cisplatin in vitro also resulted in upregulated intrinsic FXa and thrombin formation on platelets with a dose-dependent manner. Platelets treated with aspirin significantly decreased PCA. However, lactadherin blocked PS and inhibited the PCA approximately by 70%. Seven days after chemotherapy, PCA of platelets restored to the baseline as that before chemotherapy, indicating that within a week of chemotherapy patient platelets are highly procoagulant and effective intervention should be taken in case of thrombosis. Our results suggested that platelets after chemotherapy had elevated PCA and may contribute to the hypercoagulative state of NSCLC. Prophylactic anti-coagulant combined with anti-platelet therapy may play an inhibitory role in thrombotic complications in NSCLC.

Lung Cancer and Pulmonary Embolism: What Is the Relationship? A Review

“…Tissue factor (TF), the initiator of the clotting cascade, over expresses in lung cancer cells, which implies that TF is an activator of coagulation in the wide array of lung cancer cells 55 . In addition, platelets after chemotherapy had elevated PCA (procoagulant activity) and may contribute to the hypercoagulability of non-small cell lung cancer (NSCLC) 56 .…”

Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets

“…Although our study also argues against the use of these drugs as BH3 mimetics in platelets, it does also hint at the possibility of other cell death pathways in platelets. For example, platelet death through reactive oxygen species has been implicated for several chemotherapeutic drugs [33][34][35][36][37]. Drug-induced non-apoptotic platelet death may be an important factor in chemotherapy-related thrombosis or thrombocytopenia and should be considered as a possible toxicity in any future trials of these or related drugs in patients or animal models.…”

Altered fibrin clot properties in advanced lung cancer: impact of chemotherapy

“…Recently, it has been suggested that platelets might play an important role in hypercoagulable state development after chemotherapy (11). Platelets behind blood coagulation are involved in angiogenesis and cancer growth by secretion of multiple growth factors and chemoattractants, including platelet factor 4 (34,35).…”

“…Platelets behind blood coagulation are involved in angiogenesis and cancer growth by secretion of multiple growth factors and chemoattractants, including platelet factor 4 (34,35). In vitro experiments on platelets treated with cisplatin showed that anticancer drugs can lead to increased production of intrinsic activated factor X, followed by elevated thrombin generation and fibrin formation (11). Thrombin formation and fibrin generation were increased 1 day after chemotherapy and returned to the baseline (day 0) after one week in a model using platelet-free plasma mixed with platelets isolated from blood of lung cancer patients (11).…”

“…Shortening of clotting time, increase in antithrombin levels and thrombin-antithrombin complexes, followed by decreased plasma D-dimer, plasmin-α 2 -antiplasmin complex and fibrinogen levels have been observed in lung cancer patients during the first and the second cycle of standard anticancer therapy with a large variability of these parameters up to 3 weeks after treatment (10). Recent study has demonstrated that activated and apoptotic platelets, together with plateletderived microparticles contribute to hypercoagulable state in patients with NSCLC after chemotherapy and can be closely related to thromboembolic complications during anticancer treatment (11).…”